Arachidonic acid is the precursor of a large number of compounds possessing diverse activities. Known products of arachidonic acid include the prostaglandin thromboxanes, leukotrienes and hydroxyeicosanoids. One metabolite of arachidonic acid, prostaglandin E2 (PGE2), has been implicated as a mediator of hypercalcemia associated with certain lung cancers. The luekotrienes participate in the initiation of immune and inflammatory responses and thus could play a role in host defense mechanisms in human lung cancer. Studies of the metabolism or arachidonic acid were undertaken to determine the pathways of arachidonic acid metabolism in human lung cancer cells and the relevance of arachidonate metabolism in human lung cancer. Non-small cell carcinomas of the lung (NSCCL) and small cell carcinomas of the lung (SCCL) were incubated with either 14C-labeled arachidonic acid or with 14C-labeled arachidonic acid in the presence of the calcium ionophore A23187. The major prostaglandin endoperoxide synthetase (PES) metabolite isolated from NSCCL has been tenatatively identified as PGE2. SCCL do not appear to contain significant levels of PES. Analysis of the extracts from SCCL and NSCCL for the presence of lipoxygenase products of arachidonic acid are being performed. Further studies of the metabolism of arachidonic acid by human cancer cells will continue to determine the regulation and extent of arachidonic acid metabolism in the presence and absence of different inhibitors and stimulators of the various pathways of arachidonate metabolism. Additional studies in tumor-bearing nude mice will be performed to determine whether or not the profile of arachidonate metabolism in human lung cells in vitro accurately reflect arachidonate metabolism in vivo.